The role of genetic variants in genes regulating the oxytocin–vasopressin neurohumoral system in childhood-onset aggression
Abstract
OBJECTIVE: The genetic etiology of aggressive behaviors remains elusive, but growing evidence suggests that they are heritable, and certain genetic variants have been implicated as contributing factors. The oxytocin-vasopressin (OXT-AVP) neurohumoral system has recently been implicated in social behaviors. Oxytocin, especially, has been linked to prosocial behaviors such as trust and social bonds. Hence, the aim of this study was to determine whether genes regulating this system were also associated with childhood-onset aggressive behaviors. METHODS: Our sample included 182 White children showing extreme, persistent, and pervasive aggressive behavior. These cases were matched with 182 White controls on the basis of sex and age. We used PCR to determine the genotype for 28 single nucleotide polymorphisms within eight genes regulating the OXT-AVP system, including CD38 polymorphisms. Genotypic analyses were carried out using STATA, whereas differences in haplotypic and allelic frequencies were analyzed using Unphased. RESULTS: None of the results reached significance after correction for multiple testing. However, nominally significant allelic effects were observed for OXTR rs6770632T (P=0.028) and AVPR1A rs11174811G (P=0.040) in females, and OXTR rs237898A (P=0.006), rs237902C (P=0.007), and AVP rs3761249A (P=0.008) in males. CONCLUSION: Genetic variants regulating the OXT-AVP system may be associated with childhood-onset aggression.
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The rs2282018G-rs3761249C haplotype was over-represented in male cases (window p = 0.012, haplotype-specific p = 0.011).
“rs2282018G-rs3761249C haplotype over-represented in male cases (window p = 0.012, haplotype-specific p = 0.011)”
From Genetics of child aggression, a systematic review (2024) · cites this paper as Malik [100]
The haplotype rs6770632T-rs1042778A was over-represented in female cases (window p = 0.014, haplotype-specific p = 0.081).
“Haplotype rs6770632T-rs1042778A over-represented in female cases (window p = 0.014, haplotype-specific p = 0.081)”
From Genetics of child aggression, a systematic review (2024) · cites this paper as Malik [100]
In females, AVPR1A rs11174811 G allele was over-represented in female cases (p = 0.04).
“In females: AVPR1A rs11174811 G allele was over-represented in female cases (p = 0.04)”
From Genetics of child aggression, a systematic review (2024) · cites this paper as Malik [100]
OXTR rs237902 C allele (p = 0.007) and CC genotype (p = 0.021) were over-represented in male cases.
“OXTR rs237902 C allele (p = 0.007) and CC genotype (p = 0.021) over-represented in male cases”
From Genetics of child aggression, a systematic review (2024) · cites this paper as Malik [100]
The AVP rs1410713T-rs2740204T haplotype was over-represented in male cases (window P = 0.035, haplotype-specific p = 0.013).
“AVP rs1410713T-rs2740204T haplotype over-represented in male cases (window P = 0.035, haplotype-specific p = 0.013)”
From Genetics of child aggression, a systematic review (2024) · cites this paper as Malik [100]
In males, rs237898 A allele (p = 0.006) and the AA genotype (p = 0.033) were over-represented in cases.
“In males: rs237898 A allele (p = 0.006) and the AA genotype over-represented in cases (p = 0.033)”
From Genetics of child aggression, a systematic review (2024) · cites this paper as Malik [100]
OXTR rs237898 A-allele was over-represented in cases (p = 0.018).
“OXTR rs237898 A-allele over-represented in cases (p = 0.018)”
From Genetics of child aggression, a systematic review (2024) · cites this paper as Malik [100]
The haplotype consisting of OXTR rs237898A and rs237902C was over-represented in cases (window p = 0.032, haplotype-specific p = 0.010).
“haplotype consisting of OXTR rs237898A and rs237902C was over-represented in cases (window p = 0.032, haplotype-specific p = 0.010)”
From Genetics of child aggression, a systematic review (2024) · cites this paper as Malik [100]
In females, OXTR rs6770632 T allele was over-represented in cases (p = 0.028) and rs1042778 AA genotype was over-represented in cases (p = 0.048).
“In females: OXTR rs6770632 T allele over-represented in cases (p = 0.028) and rs1042778 AA genotype over-represented in cases (p = 0.048)”
From Genetics of child aggression, a systematic review (2024) · cites this paper as Malik [100]
For AVP rs3761249, the A allele was over-represented (p = 0.008) and the AA genotype was under-represented in cases (p = 0.037).
“For AVP rs3761249: A allele over-represented (p = 0.008) and AA genotype (p = 0.037) was under-represented in cases”
From Genetics of child aggression, a systematic review (2024) · cites this paper as Malik [100]
The OXTR rs237898A and rs237902C haplotype was over-represented in male cases (window p = 0.025, haplotype-specific p = 0.021).
“OXTR rs237898A and rs237902C haplotype over-represented in male cases (window p = 0.025, haplotype-specific p = 0.021)”
From Genetics of child aggression, a systematic review (2024) · cites this paper as Malik [100]
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Self-citation
- Authors
- Malik, A. I., Zai, C. C., Berall, L., Abu, Z., Din, F., Nowrouzi, B., Chen, S., & Beitchman, J. H.
- Affiliations
- Western University (CA)
- Centre for Addiction and Mental Health (CA)
- Corresponding author
- Beitchman, Joseph H.
- Venue
- Psychiatric Genetics
- Published
- 2014-10
- Volume
- 24
- Issue
- 5
- Pages
- 201-210
- ISSN
- 0955-8829 (ISSN-L)
- OpenAlex
- W2049416997
- Cited by
- 29
- References
- 29
- Citations by year
- 2024: 2 · 2022: 2 · 2021: 2 · 2020: 4 · 2019: 3 · 2018: 5 · 2017: 3 · 2016: 5 · 2015: 3
- FWCI
- 5.42
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Psychiatric Genetics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Natural Sciences and Engineering Research Council of Canada
- Topics
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Social Sciences › Psychology › Clinical Psychology › Psychopathy, Forensic Psychiatry, Sexual Offending
- Keywords
- oxytocin, vasopressin, single nucleotide polymorphisms, oxytocin receptor, AVPR1A, CD38, genetic variants, aggression, heritability, social behavior
- MeSH terms
- Adolescent, Aggression, Alleles, Child, Female, Gene Frequency, Haplotypes, Humans, Male, Oxytocin, Vasopressins, Linkage Disequilibrium, Case-Control Studies, Receptors, Vasopressin, Receptors, Oxytocin, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide
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